Porphyromonas gingivalis is an invasive anaerobe implicated in periodontal tissue destruction. While it is currently considered that the host response contributes to disease progression and may dictate the pattern and severity of the disease, virulence factors of specific bacteria of the Dental plaque including P. gingivalis also contribute to periodontal pathoses. P. gingivalis invades the highly vascularized gingival tissues, which enables the bacterium to gain access to iron sources and to avoid the host immune response. We have observed that the invasive ability of various P. gingivalis strains varies by as much as three orders of magnitude. This is most likely explained by genetic polymorphisms present on the P. gingivalis genome. Such polymorphisms reflect inter-strain heterogeneity that can be characterized using global genomic microarray-based analysis. Using such microarray-based comparative genomic hybridization (CGH) we have previously analyzed laboratory strains of P. gingivalis that have diverse invasion abilities. This analysis revealed a subset of invasion-associated genes from the P. gingivalis genome. We have also shown that P. gingivalis strains present in diseased sites have significantly greater invasive efficiencies than P. gingivalis strains from healthy sites. Consequently, our goal for this project is to screen clinical strains in order to determine if there is a direct link between genes encoding invasion-associated functions and disease. For this, we will utilize P. gingivalis strains from diseased sites and from periodontal healthy sites. It is our hypothesis that the presence of an invasion-associated subset of bacterial genes can be linked with the severity of disease. Our hypothesis will be tested by 1) testing clinical P. gingivalis isolates from diseased and healthy sites for the presence/absence of invasion-specific genes, and 2) relating the presence of specific invasion-associated genes, or sets of genes, with the clinical indices. Identification of unique disease-associated virulence factors (disease genotype) will lead to a better understanding of the genetic heterogeneity of this organism and the ability to design diagnostic tools for risk assessment and therapies for chronic and aggressive periodontitis. This approach will also likely identify moieties involved in cross talk between invasive clinical strains and the host tissue. Such information will further facilitate the development of novel defined molecular approaches for the treatment of periodontitis. [unreadable] [unreadable] [unreadable]